Role of Hepatic Artery Infusion Chemotherapy in Treatment of Initially Unresectable Colorectal Liver Metastases: A Review.

Importance: Although liver metastasis develops in more than half of patients with colorectal cancer, only 15% to 20% of these patients have resectable liver metastasis at presentation. Moreover, patients with initially unresectable colorectal liver metastasis (IU-CRLM) who progress on first-line systemic chemotherapy have limited treatment options. Hepatic arterial infusion chemotherapy (HAIC), in combination with systemic chemotherapy, leverages a multimodality approach to achieving control of hepatic disease and/or expanding resectability in patients with liver-only disease or liver-dominant disease. Observations: Intra-arterial delivery of agents with high first-pass hepatic extraction (eg, floxuridine) limits systemic toxic effects and allows for administration of systemic chemotherapy at near-full doses. Hepatic arterial infusion chemotherapy in conjunction with systemic chemotherapy augments response rates up to 92% in patients who are chemotherapy naive, and up to 85% in pretreated patients with IU-CRLM. In turn, these responses translate into encouraging rates of conversion to resectability (CTR). Prospective trials have reported CTR rates as high as 52% in heavily pretreated patients with IU-CRLM who have an extensive hepatic disease burden. As such, CTR remains a compelling indication for liver-directed chemotherapy in this subset of patients. This review discusses the biological rationale for HAIC, evolution of rational combinations with systemic chemotherapy, contemporary evidence for CTR using HAIC and systemic chemotherapy, juxtaposition with rates of CTR using systemic chemotherapy alone, and morbidity and toxic effect profiles of HAIC. Conclusions and Relevance: The argument is made for consideration of earlier initiation of HAIC in patients with IU-CRLM who are chemotherapy naive and for adoption of HAIC strategies to augment rates of resectability in patients who have failed first-line systemic chemotherapy before proceeding to second-line or third-line regimens.